The objective of this program project grant is to study the relation between hepatitis B virus and primary hepatocelllular carcinoma (PHC). The several stages of events that may lead to cancer are being studied by testing hypotheses generated from previous work. These include: 1) maternal transmission of HBV; 2) differential dissemination and responses to HBV among family members; 3) development and maintenance of the HBV chronic carrier state; 4) development of cirrhosis; 5) development of PHC. The eventual objective is the design of strategies for prevention of PHC. A search for viruses similar to HBV that also may be involved in the pathogenesis of human cancer is being carried out.